Selection of Device, Administration of Bronchodilator, and Evaluation of Response to Therapy in Mechanically Ventilated Patients

AARC Clinical Practice Guideline

BDMV 1.0 PROCEDURE: mechanically ventilated adult patients (1.0-15.3 Device selection, bronchodilator administration, %) compared to nonintubated, ambulatory and evaluation of response to therapy during me- adult subjects in ambulatory adult patients (10- chanical ventilation. The reader is referred to previ- 14%).22 ously published Guidelines addressing aspects of 2.3.1 In-vivo studies of aerosol deposition aerosol administration and delivery.1-4 from nebulizers during mechanical ventilation report 1.2%,23 2.22%,24 2.9%,25 and BDMV 2.0 DESCRIPTION: 15.3%26 in adults, and 0.22% in infants.27 The selection of a device and strategy for adminis- Similar studies using MDI reported 6- tration, the administration, and the evaluation of re- 11%23,28 in adults and 0.9 in infants.27 sponse of patients to bronchodilator aerosol during 2.3.2 Factors that affect lower respiratory mechanical ventilation. tract deposition include: aerosol device selected,7,10,23,24,29 how it is operated,24,26,30-32 2.1 Devices include metered dose inhaler its placement in relation to the ventilator (MDI) with adapter and chamber or inline circuit/patient,33 the ventilator selected,34 elbow and catheter; pneumatic nebulizer; small the ventilator settings and mode of venti- volume nebulizer (SVN) large volume nebuliz- lation,35 humidity,32,35 drug formulation, er (LVN); ultrasonic nebulizer. (Although expe- drug dose, and caliber of the airway.29,36-38 rience suggests that inhalers that dispense dry 2.3.3 Assessment is necessary to deter- powder are not suitable for use in ventilator cir- mine the appropriate dose, optimal fre- cuits, a recent bench study reports positive re- quency of administration, and overall results and suggests clinical trials.5 Such use can- sponse to therapy.7,39 An empirical trial of not yet be recommended.) bronchodilator is recommended in any 2.2 Aerosolized bronchodilators have been mechanically ventilated patient in whom shown to be effective in adults, children, and a potential indication exists.40 infants receiving mechanical ventilation.6-21 In- 2.4 Because delivery is reduced, increased haled beta-adrenergic7-17 and anticholinergic doses may be required to provide desired or op- bronchodilators17,18 are effectiveRETIRED in mechanical- timal effect. Patients should be monitored to ly ventilated patients. Inhaled isoproterenol hy- determine effect of dose and to support initial drochloride,15,16 isoetharine mesylate,17 metapro- and continued treatment.7-10,32. terenol sulfate,18 fenoterol,19 and albuterol7-12,14 can all produce clinically important bronchodi- BDMV3.0 SETTING: lation. In ventilator-supported COPD patients, Aerosolized bronchodilator therapy via mechanical fenoterol in combination with ipratropium bro- ventilator can be provided in a number of settings mide was more effective than ipratropium including: hospital, home, and subacute or extend- alone.14 Inhaled beta adrenergic and anticholin- ed care facility. ergic drugs are effective in ventilated infants and neonates with acute, subacute, and chronic BDMV 4.0 INDICATIONS: lung disease.18-20 Bronchodilator aerosol administration and evalua- 2.3 Aerosol deposition in the lung has, in gen- tion of response are indicated whenever bron- eral, been shown to be reduced in intubated, choconstriction or increased airways resistance is

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documented or suspected in patients during me- 6.6.1 Addition of gas to the ventilator cir- chanical ventilation: cuit from a nebulizer may increase volumes, flows, and peak airway pressures, BDMV 5.0 CONTRAINDICATIONS: thus altering the intended pattern of venti- 5.1 Some assessment maneuvers may be con- lation. Ventilator setting adjustments traindicated for patients in extremis (eg, pro- made to accommodate the additional gas longed inspiratory pause for patients with high flow during nebulization must be reset at auto-PEEP). the end of the treatment. 5.2 Certain medications may be contraindicated 6.6.2 Addition of gas from a nebulizer in some patients. Consult the package insert for into the ventilator circuit may result in the product-specific contraindications. patient’s becoming unable to trigger the ventilator during nebulization,47 leading to BDMV 6.0 HAZARDS/COMPLICATIONS: hypoventilation. 6.1 Specific assessment procedures may have 6.7 At least one early anecdotal report de- inherent hazards or complications: (eg, inspira- scribed cardiac toxicity due to CFCs used as tory pause, expiratory pause).41-44 propellants in MDIs.48 Adverse cardiac effects 6.2 Inappropriate device selection or inappro- are unlikely to occur with doses recommended priate use of device and/or technique variables in clinical practice because of the short half life may result in underdosing.7 of CFCs in the blood (< 40 s), particularly when 6.3 Device malfunction may result in reduced at least a short interval is maintained between drug delivery and may possibly compromise successive doses.49 the integrity of the ventilator circuit.45,46 6.4 Complications of specific pharmacologic BDMV 7.0 LIMITATIONS OF PROCEDURE agents. Higher doses of beta agonists delivered OR DEVICE: by an MDI or nebulizer may cause adverse ef- 7.1 During mechanical ventilation, the deposi- fects secondary to systemic absorption of the tion of drug to the lower respiratory tract is re- drug or propellants. The potential for hy- duced. Doses should be adjusted to compensate pokalemia and atrial and ventricular dysrhyth- for reduced delivery. Variables should be opti- mias may exist with high doses in critically ill mized to enhance medication delivery. patients.47-49 7.2 Ventilator modes and settings can affect de- 6.5 Aerosol medication, propellants, or cold, position. Lung-model studies suggest that low dry gas that bypasses the natural upper respira- inspiratory flows, use of decelerating flow in- tory tract may cause bronchospasm or irritation stead of square wave, tidal volume > 500 mL, of the airway.47-50 Although the efficiency of and increased duty cycle (inspiratory phase) are aerosol delivery from an MDI can be increased all associated with improved aerosol deposi- by actuating the canister into a narrow gauge tion.24,26,30,31 Spontaneous inspiration through the catheter with the catheter positionedRETIRED at the end ventilator circuit increased lung deposition of the endotracheal tube. A study in rabbits29 has compared to controlled, assist/control and pres- shown that such introduction produces necro- sure support ventilation.35 tizing inflammation and mucosal ulceration, 7.3 Humidification of inspired gas during me- probably from the topical effect of the oleic chanical ventilation reduces aerosol deposition to acid used for its surfactant property and the the lower respiratory tract by approximately chlorofluorocarbons (CFCs). Such administra- 40%.32,35 Because these in vitro studies suggest tion is not recommended. The results of further that humidity markedly decreases aerosol, the al- study are needed to support or condemn this ternatives are to bypass the humidifier during practice. aerosol therapy, which may dry the airway and 6.6 The aerosol device or adapter used and offset the effect of the increased delivery, or to re- technique of operation may affect ventilator tain the humidifier and increase the dose of bron- performance characteristics and/or alter the chodilator. It is probably better to retain the hu- sensitivity of the alarm systems. midifier and increase the dose of bronchodilator.

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7.4 Placement of the aerosol device in the ven- vivo experiments have associated tilator circuit affects the amount of drug deliv- endothelial damage at the carina in ered to the lungs.33. Placing the nebulizer 30 cm response to temperature and ingredi- from the endotracheal tube is more efficient ents (oleic acid) of the aerosol.50 In- than placing it between the patient Y and the sufficient data are available to sup- endotracheal tube because the tubing acts as a port clinical use of such devices at reservoir for accumulation of aerosol between this time.50,54 inspirations.15,16,28 If an artificial nose is in use, it 7.6.1.4 MDI actuation is performed should be removed during aerosol administra- manually and should be synchro- tion.51 nized with the beginning of inspira- 7.5 Coordination of aerosol generation with tion.32,35 Actuating an MDI out of ventilator triggering (initiation of inspiratory synchrony with the inspiratory air- gas flow) improves delivery of drug to the flow has been shown to result in lung.31 negligible aerosol delivery to the 7.6 Limitation of specific devices lower airway.32 7.6.1 MDI 7.6.2 Small volume nebulizer The MDI cannot be used for the mechani- 7.6.2.1 Differences in placement of cally ventilated patient with the actuator nebulizer in the ventilator circuit can designed for use by the spontaneously result in large variances in drug de- breathing patient with a natural airway. livered to the lung.33 An actuator designed specifically for me- 7.6.2.2 Mass median aerodynamic chanical ventilation is required for actua- diameter (MMAD) and time re- tion of an MDI into the ventilator circuit. quired for treatment may vary with Accessory device adapter design affects type of nebulizer, different models aerosol delivery and the amount of drug of the same type, and gas source, available to the lung.28,52,53 pressure, and flow. 7.6.1.1 Chamber-style adapter. Both 7.6.2.3 Gas flow and the pressure in vitro and in vivo 28,52,53 have found driving a pneumatic nebulizer may that the combination of an MDI and change particle size characteristics a chamber device results in a four- to and drug output.55-59 When gas flow sixfold increase in delivery of driving the nebulizer is from a sec- aerosol over MDI actuation into an ondary gas source (other than the elbow connector (without chamber) ventilator), the volumes, flows, and attached directly to the endotracheal pressures delivered by the ventilator tube or into an inline adapter with- to the patient are altered.34 out chamber. This correlates with 7.6.2.4 Nebulizer output and effi- clinical response studiesRETIRED showing ciency are affected by fill volume clinical response with as little as 4 and flow.55-60 puffs of albuterol10 whereas an 7.6.2.5 Nebulizers in line with the elbow adapter demonstrated no re- ventilator circuit tend to collect con- sponse with 100 actuations of al- densate when not in use and should buterol.7 be removed from ventilator circuit 7.6.1.2 Small-gauge adapters with between treatments. closed suction devices. No pub- 7.6.2.6 Nebulizers are vulnerable to lished data support the use of these contamination, posing consequent adapters. increased risk for nosocomial infec- 7.6.1.3 Small-gauge tracheal tion.61,62 catheter adapter. Although initial ex- 7.6.2.7 Because of the relatively periments suggest high-dose deliv- large amount of medication that is ery to the lung (> 90% in vitro), in exhaled by the patient or that by-

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passes the patient into the expiratory 9.1.1.2 Ascertain clinical indicators or limb, placing a filter in the expirato- need for therapy ry limb may reduce drug deposition 9.1.1.3 Identify possible contraindica- on pneumotachographs or transduc- tions ers and thus help maintain their ac- 9.1.2 During therapy, identify: curacy. 9.1.2.1 adverse responses; 7.6.4 LVN: 9.1.2.2 any clinical change from base- 7.6.4.1 Concentration of medication line; delivered may vary during treatment 9.1.2.3 lack of response. due to changing dilution of medica- 9.1.3 Following therapy, identify tion.63-66 9.1.3.1 adverse responses and 7.6.4.2 Close monitoring is required. 9.1.3.2 presence or absence of thera- 7.6.4.3 Few units meet MMAD of 1-3 peutic responses microns.67 9.1.4 For trend analysis, identify: 7.6.4.4 Devices are vulnerable to con- 9.1.4.1 change in patient baseline; tamination. 9.1.4.2 need to modify dose; 7.6.5 USN 9.1.4.3 need to modify therapy; Although it has been suggested that the 9.1.4.4 need to discontinue; use of the USN may lead to bronchodila- 9.1.4.5 apparent changes in tor delivery greater than with a compara- bronchial responsiveness. gle dose by pneumatic nebulizer, evidence 9.2 Action based on result of assessment and is lacking.68-70 evaluation: 9.2.1 increase or decrease dose; BDMV 8.0 ASSESSMENT OF NEED: 9.2.2 change or add medications; 8.1 The presence of one or more of the follow- 9.2.3 continue or discontinue therapy. ing in the mechanically ventilated patient sug- (Discontinuance of bronchodilator thera- gests the need for bronchodilator administra- py should be considered in patients in tion: whom no objective or subjective response 8.1.1 previous demonstrated response to is seen after repeated administration.40,71 bronchodilator; 9.3 Documentation 8.1.2 presence of auto-PEEP not eliminat- 9.3.1 Patient response to medication ed with reduced rate, increased inspirato- 9.3.1.1 Medication: type, dose, and ry flow, or decreased inspiratory to expi- time received ratory time ratio; 9.3.1.2 Responses measured including 8.1.3 increased airway resistance as evi- vital signs, lung function as reflected denced by by changes in peak inspiratory pressure 8.1.3.1 increased peak inspiratoryRETIRED pres- (PIP), plateau pressure (P ), auto- plat sure and plateau pressure difference; PEEP (PEEPi), and bedside observa- 8.1.3.2 wheezing or decreased breath tions. sounds; 9.3.1.3 Note observations relative to 8.1.3.3 intercostal and/or sternal retrac- time of administration . tions; 8.1.3.4 patient-ventilator dysynchrony. BDMV 10.0 RESOURCES 8.2 Response to therapy should be evaluated in 10.1 Equipment all patients receiving bronchodilator therapy.2 10.1.1 Ventilator with manometer and ca- pability to measure end-inspiratory and BDMV 9.0 ASSESSMENT OF OUTCOME end-expiratory pause. 9.1 Evaluation of need and response 10.1.1.1 Equipment required for mea- 9.1.1 Assessment prior to therapy: suring auto-PEEP 9.1.1.1 Establish baseline condition 10.1.1.2 Pneumotachograph for moni-

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toring pressure, flow, and volume and document measures of response es- changes at the airway. tablished by the patient’s care plan (eg, 10.1.2 Pulse oximeter use of diary and peak flow meter); 10.1.3 Stethoscope 10.2.2.2 use proper technique in ad- 10.1.4 Cardiac monitor, when available ministering medication; 10.2 Personnel:72,73 10.2.2.3 maintain and clean equipment; 10.2.1 Level II personnel—licensed or 10.2.2.4 instruct patients in proper credentialled respiratory care practitioner breathing patterns and coughing tech- (eg, RRT, RPFT, CRT) or persons with niques; documented equivalent training and abili- 10.2.2.5 modify therapy in response to ty should possess knowledge and skills to: changes in monitored variables, severi- 10.2.1.1 perform initial assessments ty of symptoms, or adverse reactions, and care for the unstable patient; and communicate any modifications 10.2.1.2 assess patient condition and with Level II provider or physician. response to therapy; 10.2.2.6 Understand and comply with 10.2.1.3 identify the indications for and Standard Precautions. effects of specific medication and 10.2.3 When mechanically ventilated pa- equipment; tients are cared for in the home, the pa- 10.2.1.4 instruct patients in proper tient, family member, or designated care- breathing patterns and coughing tech- giver providing routine maintenance ther- niques; apy must know and demonstrate ability 10.2.1.5 modify technique in response to: to adverse reactions; 10.2.3.1 monitor or measure response 10.2.1.6 modify dosages and/or fre- to bronchodilator in accordance with quency according to patient response; the patient’s care plan (eg, Pinsp, 9,11 10.2.1.7 use proper technique for ad- Pplat); ministration of aerosols. 10.2.3.2 use proper technique for ad- 10.2.1.8 perform and document results ministration of medication and use of of auscultation, inspection, and assess- devices correctly (eg, MDI with spacer, ment of vital signs; SVN, USN );11 10.2.1.9 perform, interpret, and docu- 10.2.3.3 properly use and clean equipment Pinsp - Pplat or ventilatory mechan- ment; ics 10.2.3.4 modify dosages and/or fre- 10.2.1.10 understand and comply with quency as prescribed and instructed Standard Precautions, as set forth by and assure appropriate communication the Centers for Disease Control and with physician regarding severity of Prevention (CDC). RETIREDsymptoms. 10.2.1.11 Level II personnel who care for long-term ventilator-dependent pa- BDMV 11.0 MONITORING:(bronchodilator re- tients should be able to teach family sponse) members or other designated care giver 11.1 Patient observation to assess need for and response to bron- 11.1.1 General appearance, presence of chodilators and develop, teach, and as- tremor sess self-care plans for the patient or 11.1.2 Use of accessory muscles or pa- the family care giver. tient-ventilator dysynchrony 10.2.2 Level-I personnel—licensed or 11.2 Percussion and auscultation, including credentialled respiratory care practitioner presence or absence of wheezing33 (eg, CRT, CPFT) or person with docu- 11.3 Patient symptoms and vital signs12-14 mented equivalent training and ability to: 11.4 Improvement in dyspnea26,27 10.2.2.1 observe, measure, monitor, 11.5 Changes in SaO228 or SpO2

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11.8 Changes in exercise performance32 Nebulizers should not be used between patients 11.9 Changes in ventilator variables35 without disinfection. Nebulizers should be changed 11.9.1 Pinsp-Pplat difference or sterilized at conclusion of dose administration or 11.9.2 Inspiratory and expiratory resis- at 24-hour intervals with continuous administra- tance.(Changes in minimal inspiratory re- tion76 and whenever visibly soiled. Nebulizers sistance (Rsmin) and/or maximal inspirato- should not rinsed with tap water between treatments ry resistance (Rsmax) are being used as a research tool.10) Medications should be handled aseptically. 11.9.3 Expiratory flow, flow-volume loop 11.9.4 Auto-PEEP reduction Medications from multidose-dose sources in acute 11.10 Subjective response care facilities must be handled aseptically and dis- 11.11 Changes in sputum clearance carded after 24 hours. 11.12 Changes in arterial blood gas values 11.13 Adverse response to drug Synopsis

BDMV 12.0 FREQUENCY: Recommendations for Bronchodilator Delivery 12.1 Acute, unstable patient during Mechanical Ventilation 12.1.1 Full assessment with first treatment 1. Ventilator Settings 12.1.2 Assessment with documentation of Caution: If gas other than that from the ventila- all appropriate monitored variables before tor is used to power the nebulizer, that flow may af- and after each treatment, with monitoring fect the delivered tidal volume, the inspired oxygen of breath sounds, vital signs, side effects concentration, and the patient’s ability to trigger the 9 during therapy, Pinsp and Pplat ventilator. It may be necessary to decrease the set 12.1.3 Frequency of physical exam and tidal volume. For a patient triggering the ventilator, Pinsp - Pplat should be based on patient sta- the rate may need to be increased to maintain an ap- tus. propriate minute ventilation 12.1.4 SpO2 should be monitored continu- Recommendations: Consider the following, if ously, if available. not otherwise contraindicated—(1) Use of a tidal 12.1.5 Continue assessment at each level volume > 500 mL for adults; (2) addition of an in- of dose to optimal response for patient. spiratory pause or lower flows, which may improve 12.2 Stable patient pulmonary deposition of aerosol; however clinical 12.2.1 The Pinsp-Pplat difference should be judgment and patient evaluation must assure that measured before and after bronchodilator the patient’s inspiratory flow demands are met (ie, therapy. the inspiratory-to-expiratory-time ratio is subjec- 12.2.1.1 Periodic reevaluation for re- tively and physiologically appropriate and auto- sponse to therapy. RETIREDPEEP is not increased);(3) because spontaneous 12.2.1.2 Standard frequency with al- breaths may improve aerosol deliver, spontaneous buterol and ipratropium should be every 4 breathing should not be suppressed during aerosol hours and/or as required. therapy unless the patient’s ability to trigger the 12.2.1.3 Other drugs, frequency based on ventilator is affected. manufacturer recommendation (ie, salme- 2. Humidifier Use terol every 12 hours). Caution: Use of an external gas source to power the nebulizer may cause heated circuit malfunction; 13.0 INFECTION CONTROL: (2) an artificial nose, or heat-and-moisture ex- CDC Standard Precautions as CDC recommenda- changer, must be removed before aerosol therapy is tions to control exposure to tuberculosis and droplet begun. nuclei.74,75 Recommendations: Although humidified gas has been shown to reduce aerosol delivery by as

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much as 40%, the humidifier should remain inline Respir Care 1992;37(8):891-897. 2. American Association for Respiratory Care. AARC Clinical because of the risks associated with the delivery of practice guideline: delivery of aerosols to the upper air- dry gas. An increase in aerosol dose may compen- way. Respir Care 1994;39(8)803-807. sate for this effect. 3. American Association for Respiratory Care. AARC Clinical 3. Metered Dose Inhaler Use practice guideline: assessing response to bronchodilator Caution: The dose delivered from an MDI is re- therapy at point of care. Respir Care 1995;40(12):1300- 1307. duced significantly by failure to actuate the inhaler 4. American Association for Respiratory Care. AARC Clinical with the onset of inspiration. practice guideline: selection of a device for delivery of Recommendations: (1) Use an MDI fitted with a aerosol to the lung parenchyma. Respir Care chamber device; (2) actuate the MDI manually and 1996;41(7):647-653. synchronize actuation with the beginning of inspi- 5. Everard ML, Devadason SG, LeSouef PN. In vitro assessment of drug delivery through an endotracheal tube ration; (3) 4 puffs are the usual recommended dose; using a dry powder inhaler delivery system. Thorax however, greater doses may be required when clini- 1996;51(1):75-77. cal monitoring of the patient suggests incomplete or 6. Gross NJ,. Jenne JW, Hess D. Bronchodilator therapy. In: inadequate response. M.J. Tobin, editor. Principles and Practice of Mechani- 4. Nebulizer Use cal Ventilation. McGraw Hill Publishing Co., New York 1994:1077-1123. Cautions: (1) Do not leave athe nebulizer inline 7. Manthous, CA, Hall JB, Schmidt,GA, Wood LDH. Me- between aerosol treatments; (2) change the nebuliz- tered-dose inhaler versus nebulized albuterol in mechan- er every 24 hours; (3) do not rinse the nebulizer ically ventilated patients. Am Rev Respir Dis with tap water. 1993;148:1567-1570. Recommendations: (1) When possible place the 8. Manthous CA, Chatila W, Schmidt GA, Hall JB. Treatment nebulizer 30 cm from the proximal end of the endo- of bronchospasm by metered-dose inhaler albuterol in mechanically ventilated patients. Chest 1995;107:210- tracheal tube; (2) it may be necessary to add a filter 213. in the expiratory limb of the circuit to maintain ex- 9. Dhand R, Jubran A, Tobin MJ. Bronchodilator delivery by piratory flow-sensor accuracy when large doses of metered-dose inhaler in ventilator-supported patients. aerosol are delivered by nebulizer. Am J Respir Crit. Care Med 1995;151:1827-1833. 10. Dhand R, Duarte AG, Jubran A, Jenne JW, Fink JB, Fahey PJ, Tobin MJ. Dose response to bronchodilator deliv- 5. Patient Monitoring ered by metered-dose inhaler in ventilator-supported pa- Monitor the response to therapy with each treat- tients. Am J Respir Crit Care Med 1996;154:388-393. ment. 11. Gay PC, Rodarte JR, Tayyab M, Hubmayr. RD. Evaluation ¥ For volume ventilation: peak inspiratory pres- of bronchodilator responsiveness in mechanically venti- sure and the difference between peak inspirato- lated patients. Am. Rev. Respir. Dis 1987;136:880-885. 12. Gay PC, Patel HG, Nelson SB, Gilles B, Hubmayr RD. Me- ry pressure and plateau pressure; for pressure tered dose inhalers for bronchodilator delivery in intu- ventilation: tidal volume. bated, mechanically ventilated patients. Chest ¥ Auto-PEEP 1991;99:66-71. ¥ Peak expiratory flow and/or flow-volume loop 13. Wegener T, Wretman S, Sandhagen B, Nystrom S-O. Ef- RETIREDfect of ipratropium bromide aerosol on respiratory func- ¥ Breath sounds tion in patients under ventilator treatment. Acta Anes- thesiol Scand 1987;31:652-654. Bronchodilator Administration during Mechani- 14. Fernandez A, Lazaro A, Garcia A, Aragon C, Cerda E. cal Ventilation Working Group Bronchodilators in patients with chronic obstructive pulmonary disease on mechanical ventilation: utilization of Jon Nilsestuen PhD RRT, Chairman, Galveston TX metered-dose inhalers. Am Rev Respir Dis 1990;141:164-168. James Fink MS RRT, Hines IL 15. Fresoli RP, Smith RM, Young JA, Gotshall SC. Use of Dean Hess PhD RRT, Boston MA aerosol isoproterenol in an anesthesia circuit. Anesth James Volpe III Med RRT, San Diego CA Analg 1968;47:127-132. 16. Gold, MI. Treatment of bronchospasm during anesthesia. REFERENCES Anesth Analg 1975;54:783-786. 17. Sprague DH. Treatment of intraoperative bronchospasm 1. American Association for Respiratory Care. AARC Clinical with nebulized isoetharine. Anesthesiology practice guideline: selection of aerosol delivery device. 1977;46:222-224.

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18. Bernasconi M, Brandolese R, Poggi R, Manzin E, Rossi. A. 32. Diot P, Morra L, Smaldone GC. Albuterol delivery in a Dose-response effects and time course of effects of in- model of mechanical ventilation: comparison of me- haled fenoterol on respiratory mechanics and arterial tered-dose inhaler and nebulizer efficiency. Am J Respir oxygen tension in mechanically ventilated patients with Crit Care Med 1995;152:1391-1394. chronic airflow obstruction. Intensive Care Med 33. Hughes JM, Saez J. Effects of nebulizer mode and position 1990;16:108-114. in a mechanical ventilator circuit on dose efficiency. 19. Wilkie RA, Bryan MH. Effect of bronchodilators on airway Respir Care 1987;32:1131-1135. resistance in ventilator-dependent neonates with chronic 34. McPeck M, O’Riordan TG, Smaldone GC. Predicting lung disease. J Pediatr 1987;111:278-282. aerosol delivery to intubated patients: influence of 20. 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